Didemnin B (Synonyms: NSC 325319, NSC 333841) |
| Catalog No.GC49153 |
Didemnin B is a cyclic depsipeptide produced by marine tunicates that specifically binds the GTP-bound conformation of EEF1A, inhibiting its release from the ribosomal A site and preventing subsequent peptide elongation.
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Cas No.: 77327-05-0
Sample solution is provided at 25 µL, 10mM.
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Didemnin B is a cyclic depsipeptide produced by marine tunicates that specifically binds the GTP-bound conformation of EEF1A, inhibiting its release from the ribosomal A site and preventing subsequent peptide elongation.Didemnin B thereby specifically inhibits eEF1A-1 release from the ribosomal A-site, preventing peptidyl-tRNA translocation and subsequent peptide elongation. It is a potential anticancer, antiviral, and immunosuppressive agent[1,2].
Didemnin B (80 nM,48h) prevent upregulation of GRP78 protein in HepG2 cells,in association with sustained inhibition of protein synthesis[3]. The structurally unrelated cyclic peptides didemnin B and ternatin-4 bind to the eEF1A(GTP)-aa-tRNA ternary complex and inhibit translation but have different effects on protein synthesis in vitro and in vivo. By binding to a common site on eEF1A, didemnin B and ternatin-4 trap eEF1A in an intermediate state of aa-tRNA selection, preventing eEF1A release and aa-tRNA accommodation on the ribosome[5]. Didemnin B can induce apoptosis in a wide range of transformed cell lines[6].
Acute intervention with the EEF1A inhibitor, didemnin B, improves hepatic lipotoxicity in obese mice with NAFLD through mechanisms not entirely dependent on decreased food intake, suggesting a potential therapeutic strategy for this ER stress-related disease[4].Didemnin B improves hepatic steatosis, glucose tolerance, and blood lipids in obesity, in association with moderate, possibly hormetic, upregulation of pathways involved in cell stress response and energy balance in the liver[7].
References:
[1]. Marco E, MartÍn-SantamarÍa S, et,al. Structural basis for the binding of didemnins to human elongation factor eEF1A and rationale for the potent antitumor activity of these marine natural products. J Med Chem. 2004 Aug 26;47(18):4439-52. doi: 10.1021/jm0306428. PMID: 15317456.
[2]. Lee J, Currano JN, et,al. Didemnins, tamandarins and related natural products. Nat Prod Rep. 2012 Mar;29(3):404-24. doi: 10.1039/c2np00065b. Epub 2012 Jan 23. PMID: 22270031.
[3]. Stoianov AM, Robson DL, et,al. Elongation Factor 1A-1 Is a Mediator of Hepatocyte Lipotoxicity Partly through Its Canonical Function in Protein Synthesis. PLoS One. 2015 Jun 23;10(6):e0131269. doi: 10.1371/journal.pone.0131269. PMID: 26102086; PMCID: PMC4478042.
[4]. Hetherington AM, Sawyez CG, et,al. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiol Rep. 2016 Sep;4(17):e12963. doi: 10.14814/phy2.12963. PMID: 27613825; PMCID: PMC5027364.
[5]. Juette MF, Carelli JD, et,al. Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes. Elife. 2022 Oct 20;11:e81608. doi: 10.7554/eLife.81608. PMID: 36264623; PMCID: PMC9584604.
[6]. Baker MA, Grubb DR, et,al. Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells. Apoptosis. 2002 Oct;7(5):407-12. doi: 10.1023/a:1020078907108. PMID: 12207173.
[7]. Wilson RB, Chen YJ, et,al.The marine compound and elongation factor 1A1 inhibitor, didemnin B, provides benefit in western diet-induced non-alcoholic fatty liver disease. Pharmacol Res. 2020 Nov;161:105208. doi: 10.1016/j.phrs.2020.105208. Epub 2020 Sep 22. PMID: 32977024.
| Molecular Dynamics of the Ternary Complexes eEF1A·GTP·Mg2+ and Didemnin B·eEF1A·GTP·Mg2+ [1]: | |
Preparation Method | The eEF1A·GTP·Mg2+ and Didemnin B·eEF1A·GTP·Mg2+ complexes were solvated by adding a spherical shell of ∼3000 TIP3P water molecules centered at CG1 of Leu77. The radius of this water shell was 35 Å to ensure the solvation of the interdomain cleft in both complexes. These water molecules were first energy-minimized, and then both waters and all protein residues were allowed to relax. In each case, 1000 steps of steepest descent were followed by 2000 steps of conjugate gradient energy minimization. The final coordinate sets were used as input for the subsequent MD simulations. SHAKE was used for all bonds, and the integration time step was 2 fs. Only the water molecules were free to move for the first 100 ps. For the remaining 2000 ps the whole system was allowed to relax. |
Applications | Didemnin B specifically binds GTP-bound eEF1A-1, in a location between the aa-tRNA-binding and GTP-binding domains, but distinct from the actin-binding domain. Didemnin B thereby specifically inhibits eEF1A-1 release from the ribosomal A-site, preventing peptidyl-tRNA translocation and subsequent peptide elongation. |
| Cell experiment [2]: | |
Cell lines | HepG2 cells |
Preparation Method | Cells were treated with palmitate, with or without 80 nM didemnin B, followed by assessment of ER stress (6 h), protein synthesis (6-24 h), and cell death (48 h). |
Reaction Conditions | 80 nM didemnin B for 6-48 h |
Applications | Didemnin B prevent upregulation of GRP78 protein in HepG2 cells,in association with sustained inhibition of protein synthesis. |
| Animal experiment [3]: | |
Animal models | Five-week-old male C57BL/6J and leptin-deficient (ob/ob) mice on a C57BL/6J background |
Preparation Method | Used 5-week-old male C57BL/6J (lean control) and leptin-deficient ob/ob mice. All mice were fed AIN-76A diet for 4 weeks. During week 5, mice were given i.p. injections of didemnin B (50 μg/kg) or vehicle control on days 1, 4, and 7. |
Dosage form | didemnin B (50 μg/kg) on days 1, 4, and 7( i.p. injections) |
Applications | Didemnin B treatment modestly reduces food consumption in obese mice. |
References: | |
| Cas No. | 77327-05-0 | SDF | |
| Synonyms | NSC 325319, NSC 333841 | ||
| Canonical SMILES | O=C1N2[C@](CCC2)([H])C(N([C@H](C(O[C@@H]([C@@H](C(N[C@]([C@H](CC(O[C@H](C([C@@H](C(N[C@H]1CC(C)C)=O)C)=O)C(C)C)=O)O)([H])[C@@H](C)CC)=O)NC([C@@H](CC(C)C)N(C)C([C@H]3N(C([C@@H](O)C)=O)CCC3)=O)=O)C)=O)CC4=CC=C(C=C4)OC)C)=O | ||
| Formula | C57H89N7O15 | M.Wt | 1112.4 |
| Solubility | Acetonitrile: 1 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.899 mL | 4.4948 mL | 8.9896 mL |
| 5 mM | 0.1798 mL | 0.899 mL | 1.7979 mL |
| 10 mM | 0.0899 mL | 0.4495 mL | 0.899 mL |
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Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)
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